Extracorporeal Circulation With Low Systemic Heparinization During Lung Transplantation F. Pugliese, F. Ruberto, V. Ferrazza, K. Bruno, S. Martelli, P. Celli, S. Perrella, G. Aimi, D. Diso, M. Anile, F. Venuta, G.F. Coloni, and P. Pietropaoli ABSTRACT Background. Some lung transplantation (LT) recipients suffer from pulmonary hypertension and right ventricular dysfunction or failure requiring extracorporeal circulation (ECC) to avoid catastrophic complications during surgery. The extracorporeal support usually requires systemic heparinization which is potentially associated with important side effects. We performed eight LT using preheparinized ECC circuits and an oxygenator associated with a lower level of systemic heparinization without evidence of perioperative complications. Patients and Methods. From May 2002 to May 2005, 8 patients (5 men and 3 women) of mean age 22.5 ⫾ 9.5 years underwent bilateral sequential lung transplantation (BSLT) for cystic fibrosis (n ⫽ 6) or idiopathic pulmonary fibrosis (n ⫽ 2). All procedures were performed with ECC through a femoro-femoral veno-arterial bypass with preheparinized circuits and an oxygenator. Results. No intraoperative mortality occurred. The mean ECC time was 147.8 ⫾ 31.3 minutes and the mean heparin administered was 3525 ⫾ 969.16 UI. No coagulopathy or thrombotic events were observed perioperatively. Conclusions. Our study confirmed the efficacy and safety of prehepanized circuits and oxygenator for femoro-femoral veno-arterial bypass during LT for patients with severe pulmonary hypertension requiring ECC.
L
UNG TRANSPLANTATION (LT) is currently considered the only therapy currently available for end-stage pulmonary disease. At the end of 2002, 3756 procedures had been reported to the international registry.1 Patients with primary or secondary pulmonary hypertension (PH) with right ventricular dysfunction or failure are considered at increased risk for morbidity and mortality during the pulmonary artery clamping phase,2 usually requiring institution of extracorporeal support. The extracorporeal circulation (ECC) is associated with several side effects, including those related to systemic heparinization such as heparin-induced thrombocytopenia and bleeding.3 We evaluated the efficacy and safety of preheparinized circuits and oxygenator with low systemic heparinization in patients undergoing LT with ECC. PATIENTS AND METHODS From May 2002 to May 2005, 8 patients (5 men and 3 women) of mean age 22.5 ⫾ 9.5 years and mean weight 48.2 ⫾ 10.6 kg
underwent bilateral sequential lung transplantation (BSLT) for cystic fibrosis (n ⫽ 6) or idiopathic pulmonary fibrosis (n ⫽ 2); they all required institution of ECC. PH was defined by a mean resting pulmonary artery pressure (mPAP) ⱖ 25 mm Hg and pulmonary wedge pressure (PWP) ⱕ 12 mm Hg during right heart catheterization. All procedures were performed using an ECC through a femoro-femoral veno-arterial bypass with a Medtronic bio-pump (Medtronics, Minneapolis, Minn, United States) using preheparinized circuits and an oxygenator (Quadrox, Jostra, Maquet, Germany) allowing low systemic heparinization. The venous cannula was placed in the femoral vein and pushed up to the right
From the Dipartimento di Scienze Anestesiologiche, Medicina Critica e Terapia del Dolore (F.P., F.R., V.F., K.B., S.M., P.C., S.P., D.D., M.A., F.V., P.P.), the Tecnico Perfusionista, Dipartimento Trapianti d’Organo Paride Stefanini (G.A.), and the Cattedra di Chirurgia Toracica (F.V., G.F.C.), Universita’ Degli Studi di Roma “La Sapienza,” Roma, Italia. Address reprint requests to Dr Francesco Pugliese, Largo Temistocle Solera 7/10, 00199 Roma, Italia. E-mail:
[email protected]
© 2006 by Elsevier Inc. All rights reserved. 360 Park Avenue South, New York, NY 10010-1710
0041-1345/06/$–see front matter doi:10.1016/j.transproceed.2006.02.145
Transplantation Proceedings, 38, 1167–1168 (2006)
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PUGLIESE, RUBERTO, FERRAZZA ET AL Table 1. Hemodynamic Variables and Drugs Administered During BSLT First Lung
mAP (mm Hg) mPAP (mm Hg) CVP (mm Hg) PWP (mm Hg) CI (L/min/m2) ECC (L/min/m2) Diuresis (mL/h) Norepinephrine (g/kg/min) Dobutamine (g/kg/min) PGE1 (ng/kg/min) iNO (ppm)
Second Lung
Preclamp
Clamp
Declamp
Preclamp
Clamp
Declamp
65 ⫾ 11 38 ⫾ 12 7⫾3 18 ⫾ 5 4.2 ⫾ 1.6 ⬙ 80 ⫾ 12 ⬙ 5⫾0 ⬙ ⬙
55 ⫾ 12 45 ⫾ 11 11 ⫾ 4 15 ⫾ 5 2.6 ⫾ 1 1.5 ⫾ 0.8 100 ⫾ 22 0.5 ⫾ 0.3 5⫾0 20 ⫾ 0 10 ⫾ 0
61 ⫾ 7 28 ⫾ 7 6⫾3 16 ⫾ 5 2.5 ⫾ 0.9 1.8 ⫾ 0.7 90 ⫾ 13 0.4 ⫾ 0.2 5⫾0 20 ⫾ 0 10 ⫾ 0
62 ⫾ 5 33 ⫾ 5 7⫾3 16 ⫾ 4 2.4 ⫾ 0.8 1.7 ⫾ 0.5 95 ⫾ 12 0.3 ⫾ 0.1 5⫾0 20 ⫾ 0 10 ⫾ 0
54 ⫾ 8 38 ⫾ 4 10 ⫾ 5 18 ⫾ 5 2.3 ⫾ 0.9 1.7 ⫾ 0.5 100 ⫾ 13 0.3 ⫾ 0.1 5⫾0 20 ⫾ 0 10 ⫾ 0
74 ⫾ 8 26 ⫾ 3 8⫾2 11 ⫾ 5 3.9 ⫾ 1 ⬙ 120 ⫾ 15 0.05 ⫾ 0.01 5⫾0 20 ⫾ 0 10 ⫾ 0
Abbreviations: mAP, mean arterial pressure; mPAP, mean pulmonary arterial pressure; CVP, central venous pressure; PWP, pulmonary wedge pressure; CI cardiac index; ECC, extracorporeal circulation; PGE1, prostaglandine iNO, inhaled nitric oxide.
atrium; the arterial cannula was placed in the femoral artery and pushed up to the origin of the iliac artery. The ECC started just before pulmonary artery clamping (of the first lung) and stopped after declamping the second lung, when the hemodynamics were stable. An initial flow of 50% of the preclamping cardiac output was subsequently modified according to the hemodynamic parameters. The activated coagulation time (ACT) target value was 200 seconds4 and repeated boluses of 20 UI/kg of heparin were infused to reach and mantain this value. A Swan-Ganz catheter was placed to continuously evaluate cardiac output, continuous SvO2, and hemodynamic modifications (Vigilance Monitor, Edwards Lifesciences, Irvine, Calif., United States). We recorded the hemodynamic variables, the amount of administered heparin, the ECC time, the ACT mean value, the number of blood units transfused, and all complications including coagulopathy and thrombotic events. In all BSLT patients we administered norepinephrine, dobutamine, PGE1, and inhaled nitric oxide (iNO).
RESULTS
No intraoperative mortality was observed. The mean ECC time was 147.8 ⫾ 31.3 minutes and the mean ACT value was 219.7 ⫾ 26.35 seconds. The mean heparin administered was 3525 ⫾ 969.16 UI. Hemodynamic and drug support are reported in Table 1. No coagulopathy or thrombotic events were observed perioperatively. During surgery fresh frozen plasma (2387 ⫾ 356 mL) and blood (831 ⫾ 136 mL) were transfused to maintain an iNR ⬍ 1.6 and hemoglobin ⬎ 10 g/dL. DISCUSSION
The incidence of PH, which is around 30% in cystic fibrosis patients scheduled for transplantation, is a risk factor for death on the waiting list and for operative morbidity and mortality.5 Clamping of the pulmonary artery before pneumonectomy is the main test during LT. The possibility of the right ventricle to maintain cardiac output with an increased afterload is fundamental to avoid cardiopulmonary bypass. iNO is a potent, selective pulmonary vasodilator which decreases mPAP, pulmonary vascular resistance indexed and Qs/Qt (shunt ratio). Together with constant
drug support with dobutamine, PGE1, and norepinephrine, iNO improved pulmonary hemodynamics. However, PH was subclinical in a large percentage of these patients; isotopic ventriculography did not detect it. Heart failure and severe hemodynamic alterations are not uncommon during LC despite no preoperative history of PH. Some authors have suggested that such alterations tended to increase the risk of death.6 This observation explains the need for ECC during LT in patients with PH to avoid right ventricular stress during lung ventilation and pulmonary artery clamping. However, ECC may produce side effects, such as hemodilution, inflammatory mediator activation, and systemic heparinization. The use of heparin can lead to thrombocytopenia and bleeding requiring blood transfusion. The use of preheparinized circuits and an oxygenator allowed a drastic reduction in heparin dosage with respect to the accepted ACT value without perioperative thrombotic events. The hemodynamics as well as the right ventricular function were stable. In conclusion, consistent with previous reports,4 our study confirmed the efficacy and safety of preheparinized circuits and oxygenator during LT among patients with PH who required ECC. REFERENCES 1. OPTN/SRTR Annual Report 1993–2002. HHS/HRSA/OSP/ DOT, UNOS, URREA; 2003 2. Ueno T, Smith JA, Snell GI, et al: Bilateral sequential single lung transplantation for pulmonary hypertension and Eisenmenger’s syndrome. Ann Thorac Surg 69:381, 2000 3. Bianchini P: L’eparina e l’anticoagulazione. Circolazione extracorporea e supporti circolatori. Mattioli 1885, III Ed. 1999, p 231 4. Murphy JA, Savage CM, Alpard SK, et al: Low-dose versus high-dose heparinization during arteriovenous carbon dioxide removal. Perfusion 16:460, 2001 5. McCurry KR, Keenan RJ: Controlling perioperative morbidity and mortality after lung transplantation for pulmonary hypertension. Transplant Rev 12:209, 1998 6. Padilla J, Calvo V, Jordà C, et al: Lung transplantation in cystic fibrosis: perioperative mortality. Arch Bronconeumol 41:489, 2005
